How Ebola paralyses the immune system

Deaths in Africa from Ebola reached 1013 by August, with 1848 cases reported. The World Health Organization, which had declared the outbreak a global health emergency, gave ethical clearance to treat patients with the untested drug ZMapp. With all the activity on the ground in Africa – not to mention the amount of media coverage – it was something of a surprise to find that the specific way Ebola kills has only just been discovered.

In essence, the virus blocks what would usually be an instant response to infection, paralysing the body’s entire immune system. Gaya Amarasinghe of the Washington University School of Medicine in St Louis, Missouri, and colleagues say the breakthrough could guide the development of new treatments.

There are no vaccines for Ebola, and until recently ZMapp had only been tested in monkeys. Normally, the body responds to infections by producing a substance called interferon, which acts as a fast-track message to white blood cells, telling them to mobilise genes and proteins. Amarasinghe’s team found that the Ebola virus produces a substance called VP24, which blocks the channel through which interferon usually travels, crippling the immune system.

With its usual protective mechanisms knocked out, a cell is then defenceless against the virus. Amarasinghe says that drugs which target VP24 might provide alternative ways to combat the virus. Other virologists say that neutralising VP24 alone might not be enough because, like many other viruses, Ebola has other methods to thwart interferon’s distress signals. “The rest of the parts of the virus can still work and replicate without VP24,” says Ben Neuman of the University of Reading, UK.

Not cheap, not easy

Neuman says it might be difficult to find drugs that target VP24 exclusively without causing side effects. But he says that there are already drugs that target a similar molecule in the hepatitis C virus, called NS5A, without damaging healthy cells. “They’re astoundingly effective,” he says. “So in theory it could be done for VP24, but it won’t be cheap or easy.”

Options for treatments are now urgently needed. Liberia recently received a small amount of ZMapp, a mixture of three monoclonal antibodies, but only enough to treat two people. The company that makes the drug, Mapp Biopharmaceutical in San Diego, California, says only very limited supplies of ZMapp are available. So far it has been used on two infected US aid workers, who both showed signs of improvement. But it emerged that it had failed to save the life of a Spanish priest, Miguel Pajares, who was infected in Liberia.

The WHO declares a Public Health Emergency of International Concern when an outbreak crosses borders and poses an unusual threat. It has made such a declaration only twice before: for swine flu in 2009 and the polio resurgence in Pakistan earlier this year. The Ebola declaration asserts that “a coordinated international response” is required to stop further spread, because of “weak health systems in the most at-risk countries”.